The present invention relates to the preparation of liposomes adapted for specific organ targeting and to the liposomes so prepared.
Liposomes are synthetic lipid vesicles whose lipid bilayers serve as a model of biomembranes. Liposomes can be prepared by a various of techniques to yield vesicles of varying size and lamellar structure. They usually have a maximum diameter on the order of 100,000 .ANG. and most often have a diameter between 110 to 10,000 .ANG., bounded by a wall formed by at least one bimolecular layer (having a thickness on the order 100 .ANG.) of a compound of the general formula XY, where X is a hydrophilic polar group and Y is a hydrophobic non-polar group, the globules containing an aqueous liquid, for example and aqueous solution of at least one biologically active substance, and existing generally in the form of a colloidal dispersion in an aqueous medium such as an aqueous saline solution, in particular a 0.9% by weight sodium chloride solution.
The preparation of liposomes provides a method of encapsulation which is most practical and effective for aqueous materials as well as hydrophobic and amphipathic material and which is particularly useful for administration of biologically active substances, particularly medicaments, into living organisms, while avoiding the destruction or inactivation of the substance in the organism, for example by the action of gastric or intestinal juices, before the substances reach the site where they are required to act.
Central to this interest is an altered biodistribution of the agent to various organs, tissues or inflammatory sites.
Targeting of encapsulated material in liposomes has the advantage of increased specific activity of the agent to the specific target site, lowered exposure of other areas to the agent thereby decreasing effective toxicity of the agent and altered time course of agent delivery. Loaded vesicles, therefore, hold promise of therapeutic and diagnostic use in cancer patients. Multilamellar as well as unilamellar lipid vesicles loaded with a radiopaque agent have been shown to enhance hepatic and splenic imaging of the rat by X-ray computed tomography.
By selection of the compound of formula XY used to form the wall of the liposomes, it is possible to produce liposomes having walls which resist the degradation by various physiological processes.
Typical processes for the preparation of liposomes include placing a lipid in contact with an aqueous liquid that is desired to be encapsulate and then warming the heterogeneous mixture thus obtained at a temperature slightly above ambient temperature and then submitting the mixture to vigorous agitation following ultrasonic vibration.
Another process consists of dissolving a compound of formula XY (where X and Y are defined above), for example a lipid, in a volatile solvent, forming a film of the compound on the walls of a receptacle by evaporating the solvent from the solution thus obtained, introducing in the same receptacle the liquid which is desired to encapsulate in the liposomes, and finally submitting the liquid in the receptacle to the action of ultrasonic vibrations.
It would be highly desirable to provide a means for rendering liposomes more selective for a particular organ in order to improve their selectivity to deliver biologically active agents or contrast agents which can be detected by conventional scanning apparatus.